CATHEPSIN-B EXPRESSION IN COLORECTAL CARCINOMAS CORRELATES WITH TUMORPROGRESSION AND SHORTENED PATIENT SURVIVAL

Cathepsin B is a lysosomal cysteine proteinase that has the ability, t o degrade several extracellular matrix components at both neutral and acidic pH and has been implicated in the progression of several human and rodent tumors. We have studied the expression of cathepsin B in hu man colorectal tissues using a monospecific polyclonal rabbit antibody raised against human liver cathepsin B. In immunoblots of normal and neoplastic colorectal tissues this antibody specifically recognized on ly cathepsin B. We studied 101 cases of formalin-fixed, paraffin-embed ded tissue (15 normal mucosa, 17 adenomas, and 69 carcinomas). Epithel ial cells of normal mucosa and adenomas were either negative or showed a weak granular reactivity located in the paranuclear and apical cyto plasm of superficial cells. Small clusters of histiocytes were also po sitive in the region of the superficial area of the lamina propria. In carcinomas, increased expression of cathepsin B correlated with advan ced stage of the disease. Increased immunoreactivity of cathepsin B in malignant cells was associated with either a diffuse cytoplasmic stai ning or was polarized to the basal pole of the cells. This is in contr ast to the punctate paranuclear staining pattern observed is normal co lonic mucosal cells. In tumor stromal cells, increased expression of t he enzyme correlated with neoplastic progression. Expression of high l evels of cathepsin B in the tumor epithelial cells was associated with a significantly shorter survival of the patients. In conclusion, our results indicate that cathepsin B expression is up-regulated in human colorectal carcinomas compared with normal mucosa and adenomas and cor relates with tumor progression.